Prevalence, clinical features and treatment of depression in Parkinson’s disease: An update

Table 4 Studies on the effect of antidepressant drugs on depressive symptoms in Parkinson’s disease subjects with depression

Drug	Study design	Sample size	Study objectives	Outcomes	Adverse effects	Ref.
Fluoxetine		23	Effects of fluoxetine (up to 40 mg/d) on motor performance	20/23 patients experienced no worsening of parkinsonism		[167]
Fluoxetine, fluvoxamine, citalopram, and sertraline	Open-label prospective study	62 depressed patients with PD (without dementia or motor fluctuation) (15 patients received citalopram, 16 fluoxetine, 16 fluvoxamine, and 15 sertraline)	Effects of SSRIs on motor performance and depressive symptoms	↓↑ UPDRS scores Significant improvements in depression with all SSRIs		[168]
Fluoxetine/amitriptyline	Randomized study	77 patients with PD (37 received fluoxetine and 40 received amitriptyline)	Comparing fluoxetine (20-40 mg/d) and amitriptyline (25-75 mg/d) at low doses on depressive symptoms	Amitriptyline better controlled depression at 3, 6, 9 and 12 mo, respectively	15% abandoned amitriptyline because of side effects	[137]
Fluoxetine	Prospective, controlled, open-label study	18 patients with PD and mild depression without dementia	Influence of fluoxetine (20 mg/d) on motor functions	Significant improvements in scores of depression and Parkinson’s disability		[174]
Paroxetine			To assess the tolerability of paroxetine (20 mg once per day)	Improved depression UPDRS scores ↓↑	Reversible worsening of tremor in one patient	[171]
Paroxetine		65 outpatients with PD and depression	To assess the tolerability of paroxetine (10-20 mg once per day)	Improved depression	20% stopped paroxetine because of adverse reactions Increased “off” time and tremor in 2 patients (reversible)	[170]
Paroxetine CR/nortriptyline	Randomized, placebo controlled trial	52 patients with PD and depression	To evaluate the efficacy of paroxetine CR and nortriptyline in treating depression	Nortriptyline was superior to placebo for the change in depressive scores Paroxetine CR was not		[140]
Paroxetine/venlafaxine	Randomized, double-blind, placebo-controlled trial	115 subjects with PD	To compare efficacy and safety paroxetine and venlafaxine extended release in treating depression in PD	Both paroxetine and venlafaxine XR significantly improved depression UPDRS scores ↓↑		[173]
Citalopram		46 non-demented patients with PD. 18 depressed and 28 non-depressed	Effect of citalopram on motor and nonmotor symptoms of depressed and nondepressed patients with IPD	Improvement in mood in 15/16 patients Motor performance ↓↑ Improved bradykinesia and finger taps in patients with and without depression		[169]
Citalopram	Prospective, open label trial	10 patients with PD and major depression, without dementia	Effects of citalopram on depressive symptoms	Significant improvement in depression and in anxiety symptoms and functional impairment		[175]
Escitalopram	Open-label study	14 Parkinson’s disease patients with major depression	Effects of escitalopram on depressive symptoms	↓ in depressive symptomatology score (response and remission rates were only 21% and 14%)		[176]
Sertraline	Open-label pilot study	15 patients with PD and depression	To evaluate the safety and efficacy of sertraline to treat depression in PD	Significant improvement in depression UPDRS scores ↓↑	Side effects in 1/3 2 patients discontinued sertraline	[177]
Sertraline Sertraline		54 PD patients with depressive disorders 374 PD patients with depressive symptoms	Comparing efficacy of sertraline in the usual formulation and in the liquid oral concentrate Long-term effects of sertraline on motor status	Improved depression on both formulations Improved clinical global impression-severity of illness scale Improved UPDRS ↓ Anxiety ↓ Depression	8% discontinued medication for adverse events (gastrointestinal) Worsening of tremor in some patients	[179] [178]
Sertraline/amitriptyline	Prospective single-blind randomized study	31 patients with PD and depression	Assessment of the effect of sertraline (50 mg) or low-dose amitriptyline (25 mg) on depression and quality of life	↓ Depression by both drugs Sertraline improved quality of life ↓↑ UPDRS scores		[138]
Sertraline/pramipexole	Randomized trial	67 outpatients with PD and major depression but no motor fluctuations and/or dyskinesia	To compare pramipexole with sertraline	Both sertraline and pramipexole improved depression Pramipexole caused more recovery compared to sertraline (60.6% vs 27.3%) Pramipexole improved UPDRS motor subscore	14.7% withdrew from the sertraline group	[99]
Nefazodone/fluoxetine	A pilot randomized trial	Depressed patients with PD	To assess the effect of nefazodone on extrapyramidal symptoms in depressed PD patients	Nefazodone significantly improved UPDRS score Both nefazodone and fluoxetine were equally effective in treating depression		[185]
Trazodone	Randomized trial	20 PD patients with and without depression	To test the ability of trazodone to improve depression and motor function	Significantly improved depression Improves motor function in depressed patients		[186]
Venlafaxine	Prospective study	14 non-fluctuating PD patients with depression	To investigate the therapeutic efficacy of venlafaxine	Improved depression scores UPDRS scores ↓↑		[195]
Atomoxetine, a SNRI	Randomized placebo- controlled study	55 subjects with PD depression atomoxetine or placebo	To assess efficacy of atomoxetine (80 mg/d) in treating depression	Failed to improved depression Improved global cognition Improved daytime sleepiness		[196]
Duloxetine	Non-comparative, open-label, multi-center study	151 patients	To evaluate the tolerability, safety, and efficacy of duloxetine 60 mg once daily in PD patients with major depressive disorder	Improved depressive scores Improved activities of daily living Tremor ↓↑ Rigidity ↓↑	8.6% discontinued the study due to side effects	[197]

PD: Parkinson’s disease; SNRI: Selective norepinephrine reuptake inhibitor; UPDRS: Unified Parkinson’s disease Rating Scale.